Esophageal adenocarcinoma is the most rapidly increasing cancer among Caucasian males in Western countries. It is associated with Barrett's esophagus, a pre-malignant condition, for which current guidelines recommend both endoscopic screening and surveillance. This has resulted in increasing numbers of early adenocarcinomas being diagnosed that are potentially endoscopically curable. Although surgical resection and chemoradiation are effective in eliminating cancer, the morbidity from these treatments is substantial. The endoscopic treatment of early cancer includes endoscopic mucosal resection and photodynamic therapy. Endoscopic mucosal resection can remove the cancer containing tissue and permits accurate histological determination of tumor depth and extent. However, mucosal resection usually does not removal all of the premalignant mucosa and there has been a high incidence of cancer recurrence in the residual non-cancerous Barrett's mucosa. Our hypothesis is that endoscopic therapy can treat early esophageal adenocarcinoma. The primary aim of the study will be to determine if photodynamic therapy will be needed in addition to endoscopic mucosal resection to increase cancer free survival in patients with early adenocarcinoma. The study will involve one hundred patients with early esophageal adenocarcinoma that can be completely removed by mucosal resection. After removal of the cancer, these patients will be randomized to receive either photodynamic therapy or careful observation. A secondary aim of this study will be to determine if biomarkers that predict cancer progression including aneuploidy, loss of heterozygosity for p53 or p16 performed using novel cytological techniques can be correlated with flow cytometry performed on tissue. The third aim of this study will be to determine if these known biomarkers can be used to identify the patients that have progressive neoplasia and benefit from additional therapy. In addition to these known biomarkers, tissue will be stored from these patients to determine if other biomarkers might be useful in defining appropriate treatment groups. A fourth aim of this study will be to determine the patient's quality of life after these treatments since this is an important reason for choosing endoscopic therapy. General and disease specific health related quality of life assessments would be performed on a quarterly basis to determine their health status before, during and after treatment. The achievement of these specific aims is needed to help design future trials to determine the best strategy for treatment of early esophageal adenocarcinoma. Diagnostic and therapeutic techniques developed in this study can be applied to other gastrointestinal tumors.